Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine.
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Authors
McGrory, Claire L
Ryan, Karen M
Gallagher, Bronagh
McLoughlin, Declan M
Issue Date
2020-05-21
Type
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Language
en
Keywords
Depression , Gene expression , Ketamine , PEDF , VEGFA
Alternative Title
Abstract
Ketamine is a rapid-acting antidepressant but its mechanism remains unclear. Vascular endothelial growth factor growth factor (VEGF) has been reported in the antidepressant action of ketamine in rodents. VEGF and pigment epithelial-derived factor (PEDF) signalling are closely linked and both are dysregulated in depression. We explored the effect of a single infusion of ketamine, with midazolam as comparison, on peripheral whole blood mRNA levels of vascular endothelial growth factor A (VEGFA) and PEDF, and the VEGFA/PEDF ratio, in patients with depression.
Twenty-five patients with depression were randomised to either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions over 40 min. Blood plasma samples were taken 1 h before the first infusion and 4 h after the infusion start. mRNA was extracted and qRT-PCR performed to analyse gene expression.
Single infusions of ketamine and midazolam both decreased depression scores (F(1,21) = 102.40, p < 0.000). There was a significant group × time interaction for VEGFA mRNA levels (F(1, 21) = 5.207, p = 0.029), with ketamine increasing VEGFA levels. There was no significant effect of either ketamine or midazolam on PEDF levels. There was a significant group × time interaction for VEGFA/PEDF mRNA ratio, with ketamine alone increasing this ratio (F(1, 11) = 12.085, p = 0.005).
Patients were on psychotropic medication and continued treatment as usual throughout the study.
These preliminary results support a role for VEGF in the action of ketamine and suggest a novel role for VEGF/PEDF in the molecular response to ketamine.
Twenty-five patients with depression were randomised to either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions over 40 min. Blood plasma samples were taken 1 h before the first infusion and 4 h after the infusion start. mRNA was extracted and qRT-PCR performed to analyse gene expression.
Single infusions of ketamine and midazolam both decreased depression scores (F(1,21) = 102.40, p < 0.000). There was a significant group × time interaction for VEGFA mRNA levels (F(1, 21) = 5.207, p = 0.029), with ketamine increasing VEGFA levels. There was no significant effect of either ketamine or midazolam on PEDF levels. There was a significant group × time interaction for VEGFA/PEDF mRNA ratio, with ketamine alone increasing this ratio (F(1, 11) = 12.085, p = 0.005).
Patients were on psychotropic medication and continued treatment as usual throughout the study.
These preliminary results support a role for VEGF in the action of ketamine and suggest a novel role for VEGF/PEDF in the molecular response to ketamine.
Description
Citation
McGrory, C. L., Ryan, K. M., Gallagher, B., & McLoughlin, D. M. (2020). Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine. Journal of affective disorders, 273, 380–383. https://doi.org/10.1016/j.jad.2020.04.013
Publisher
License
Copyright © 2020 Elsevier B.V. All rights reserved.
Journal
Journal of affective disorders
Volume
273
Issue
PubMed ID
ISSN
1573-2517